5Z-7-Oxozeaenol, a natural anti-protozoan compound isolated from fungae, is a novel, potent irreversible / covalent and selective inhibitor of TAK1 and VEGF-R2 with IC50s of 8 nM and 52 nM, respectively.
Physicochemical Properties
| Molecular Formula | C19H22O7 |
| Molecular Weight | 362.37378 |
| Exact Mass | 362.137 |
| CAS # | 253863-19-3 |
| PubChem CID | 9863776 |
| Appearance | White to off-white solid powder |
| LogP | 1.6 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 26 |
| Complexity | 556 |
| Defined Atom Stereocenter Count | 3 |
| SMILES | C[C@H]1C/C=C\C(=O)[C@H]([C@H](C/C=C/C2=C(C(=CC(=C2)OC)O)C(=O)O1)O)O |
| InChi Key | NEQZWEXWOFPKOT-BYRRXHGESA-N |
| InChi Code | InChI=1S/C19H22O7/c1-11-5-3-7-14(20)18(23)15(21)8-4-6-12-9-13(25-2)10-16(22)17(12)19(24)26-11/h3-4,6-7,9-11,15,18,21-23H,5,8H2,1-2H3/b6-4+,7-3-/t11-,15-,18+/m0/s1 |
| Chemical Name | (3S,5Z,8S,9S,11E)-3,4,9,10-Tetrahydro-8,9,16-trihydroxy-14-methoxy-3-methyl-1H-2-benzoxacyclotetradecin-1,7(8H)-dione |
| Synonyms | FR-148083; L-783279; LL-Z 1640-2; FR148083; L783279; LL-Z 1640-2; 5Z-7-Oxozeaenol; 5Z 7 Oxozeaenol; 5Z7Oxozeaenol; 5-Z-7-Oxozeaenol; 5 Z 7 Oxozeaenol; 5Z7O; L-783279; 5 Z 7 O; L 783279; 5-Z-7-O; L783279; (5Z)-7-Oxozeaenol; |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | 5Z-7-Oxozeaenol exhibits strong, irreversible, and specific inhibition of TGF-β-activated kinase 1 (TAK1, IC50, 8.1 nM), while demonstrating negligible effect against MEK1 (IC50, 411 nM). By blocking TAK1 MAPK kinase kinase's catalytic activity, 5Z-7-Oxozeaenol reduces inflammation [1]. Moreover, 5Z-7-Oxozeaenol inhibits VEGF-R2 with an IC50 of 52 nM. 5Z-7-Oxozeaenol exhibits inhibitory activity with IC50 values of 110, 170, 340, 6300, and 6600 nM, respectively, against VEGF-R3, FLT3, PDGFR-β, B-RAF VE, and SRC [2]. Although 5Z-7-Oxozeaenol is a signaling-specific inhibitor rather than a direct inhibitor, it nevertheless inhibits the JNK/p38 pathway. 5Z-7-Oxozeaenol has no effect on IL-1-induced NF-kB activity in KK cells, but it reduces PMA-induced AP-1 activity in KT cells to nearly basal levels [3]. |
| References |
[1]. A resorcylic acid lactone, 5Z-7-oxozeaenol, prevents inflammation by inhibiting the catalytic activity of TAK1 MAPK kinase kinase. J Biol Chem. 2003 May 16;278(20):18485-90. [2]. Modular synthesis of radicicol A and related resorcylic acid lactones, potent kinase inhibitors. Angew Chem Int Ed Engl. 2007;46(36):6899-902. [3]. A radicicol-related macrocyclic nonaketide compound, antibiotic LL-Z1640-2, inhibits the JNK/p38 pathways in signal-specific manner. Biochem Biophys Res Commun. 1999 Apr 2;257(1):19-23. |
| Additional Infomation |
5Z-7-oxozeaenol is a macrolide that is the 7-oxo derivative of zeaenol (the 5Z stereoisomer). Isolated from Fungi, it exhibits cytotoxic, antibacterial and inhibitory activity against NF-kappaB. It has a role as a metabolite, an antibacterial agent, an antineoplastic agent and a NF-kappaB inhibitor. It is an aromatic ether, a macrolide, a member of phenols, a secondary alcohol and a secondary alpha-hydroxy ketone. 5Z-7-Oxozeaenol has been reported in Curvularia lunata with data available. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~50 mg/mL (~137.98 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.90 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.90 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7596 mL | 13.7981 mL | 27.5961 mL | |
| 5 mM | 0.5519 mL | 2.7596 mL | 5.5192 mL | |
| 10 mM | 0.2760 mL | 1.3798 mL | 2.7596 mL |